[Federal Register Volume 67, Number 163 (Thursday, August 22, 2002)]
[Rules and Regulations]
[Pages 54351-54359]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-21293]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-2002-0203; FRL-7194-3


Iprovalicarb; Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes an import tolerance for residues 
of iprovalicarb in or on grape at 2.0 parts per million (ppm). Tomen 
Agro, Inc. and Bayer Corporation requested this tolerance under the 
Federal Food, Drug, and Cosmetic Act, as amended by the Food Quality 
Protection Act of 1996.

DATES: This regulation is effective August 22, 2002. Objections and 
requests for hearings, identified by docket control number OPP-2002-
0203, must be received on or before October 21, 2002.

ADDRESSES: Written objections and hearing requests may be submitted by 
mail, in person, or by courier. Please follow the detailed instructions 
for each method as provided in Unit VI. of the SUPPLEMENTARY 
INFORMATION. To ensure proper receipt by EPA, your objections and 
hearing requests must identify docket control number OPP-2002-0203 in 
the subject line on the first page of your response.

FOR FURTHER INFORMATION CONTACT: By mail: Dennis McNeilly, Registration 
Division (7505C), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460; 
telephone number: (703) 308-6742; e-mail address: 
[email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    You may be affected by this action if you are an agricultural 
producer, food manufacturer, or pesticide manufacturer. Potentially 
affected categories and entities may include, but are not limited to:

[[Page 54352]]



------------------------------------------------------------------------
                                                 Examples of Potentially
             Categories                 NAICS       Affected Entities
------------------------------------------------------------------------
Industry                                    111  Crop production
                                            112  Animal production
                                            311  Food manufacturing
                                          32532  Pesticide manufacturing
------------------------------------------------------------------------

    This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. Other types of entities not listed in the table could also be 
affected. The North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether or not this action might apply to certain entities. If you have 
questions regarding the applicability of this action to a particular 
entity, consult the person listed under FOR FURTHER INFORMATION 
CONTACT.

B. How Can I Get Additional Information, Including Copies of This 
Document and Other Related Documents?

    1. Electronically. You may obtain electronic copies of this 
document, and certain other related documents that might be available 
electronically, from the EPA Internet Home Page at http://www.epa.gov/. 
To access this document, on the Home Page select ``Laws and 
Regulations'', ``Regulations and Proposed Rules,'' and then look up the 
entry for this document under the ``Federal Register--Environmental 
Documents.'' You can also go directly to the Federal Register listings 
at http://www.epa.gov/fedrgstr/. A frequently updated electronic 
version of 40 CFR part 180 is available at http://www.access.gpo.gov/nara/cfr/cfrhtml_00/ Title_40/40cfr180_00.html, a beta site currently 
under development. To access the OPPTS Harmonized Guidelines referenced 
in this document, go directly to the guidelines at http://www.epa.gov/opptsfrs/home/guidelin.htm.
    2. In person. The Agency has established an official record for 
this action under docket control number OPP-2002-0203. The official 
record consists of the documents specifically referenced in this 
action, and other information related to this action, including any 
information claimed as Confidential Business Information (CBI). This 
official record includes the documents that are physically located in 
the docket, as well as the documents that are referenced in those 
documents. The public version of the official record does not include 
any information claimed as CBI. The public version of the official 
record, which includes printed, paper versions of any electronic 
comments submitted during an applicable comment period is available for 
inspection in the Public Information and Records Integrity Branch 
(PIRIB), Rm. 119, Crystal Mall #2, 1921 Jefferson Davis Hwy., 
Arlington, VA, from 8:30 a.m. to 4 p.m., Monday through Friday, 
excluding legal holidays. The PIRIB telephone number is (703) 305-5805.

II. Background and Statutory Findings

    In the Federal Register of September 22, 2000 (65 FR 57338) (FRL-
6737-8), EPA issued a notice pursuant to section 408 of the Federal 
Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a, as amended by the 
Food Quality Protection Act of 1996 (FQPA) (Public Law 104-170), 
announcing the filing of a pesticide petition (PP 9E6020) by Tomen 
Agro, Inc; and, Bayer Corporation, 100 First Street, Suite 1700, San 
Francisco, CA 94105; and, 8400 Hawthorn Road, Kansas City, MO 64120, 
respectively. This notice included a summary of the petition prepared 
by Tomen Agro, Inc. and Bayer Corp., the registrant. Iprovalicarb is an 
amino acid amide carbamate that belongs to a new class of chemicals 
derived from natural amino acids. Iprovalicarb acts both as a contact 
and systemic fungicide and is proposed for use in the European Union 
for control of Oomycete fungi, such as downy mildew. Review of this 
import tolerance was completed in cooperation with Canada's Pest 
Management Regulatory Agency. There were no comments received in 
response to the notice of filing.
    The petition requested that 40 CFR part 180 be amended by 
establishing import tolerances for residues of the fungicide 
iprovalicarb, [2-methyl-1[[[(1S)-(4-methylphenyl) ethyl] 
amino]carbonyl] propyl]carbamic acid methylethylester, in or on grape 
and raisin at 2.0 ppm. An additional tolerance for the processed food, 
raisins, is not necessary because any residue in raisin from this use 
will be covered by the tolerance for grape.
    Section 408(b)(2)(A)(i) of the FFDCA allows EPA to establish a 
tolerance (the legal limit for a pesticide chemical residue in or on a 
food) only if EPA determines that the tolerance is ``safe.'' Section 
408(b)(2)(A)(ii) defines ``safe'' to mean that ``there is a reasonable 
certainty that no harm will result from aggregate exposure to the 
pesticide chemical residue, including all anticipated dietary exposures 
and all other exposures for which there is reliable information.'' This 
includes exposure through drinking water and in residential settings, 
but does not include occupational exposure. Section 408(b)(2)(C) 
requires EPA to give special consideration to exposure of infants and 
children to the pesticide chemical residue in establishing a tolerance 
and to ``ensure that there is a reasonable certainty that no harm will 
result to infants and children from aggregate exposure to the pesticide 
chemical residue * * *''
    EPA performs a number of analyses to determine the risks from 
aggregate exposure to pesticide residues. For further discussion of the 
regulatory requirements of section 408 and a complete description of 
the risk assessment process, see the final rule on Bifenthrin Pesticide 
Tolerances (62 FR 62961, November 26, 1997) (FRL-5754-7).

III. Aggregate Risk Assessment and Determination of Safety

    Consistent with section 408(b)(2)(D), EPA has reviewed the 
available scientific data and other relevant information in support of 
this action. EPA has sufficient data to assess the hazards of and to 
make a determination on aggregate exposure, consistent with section 
408(b)(2), for an import tolerance for residues of iprovalicarb on 
grape at 2.0 ppm. EPA's assessment of exposures and risks associated 
with establishing the tolerance follows.

A. Toxicological Profile

    EPA has evaluated the available toxicity data and considered its 
validity, completeness, and reliability as well as the relationship of 
the results of the studies to human risk. EPA has also considered 
available information concerning the variability of the sensitivities 
of major identifiable subgroups of consumers, including infants and 
children. The nature of the toxic effects caused by iprovalicarb are 
discussed in the following Table 1 as well as the no observed adverse 
effect level (NOAEL) and the lowest observed adverse effect level 
(LOAEL) from the toxicity studies reviewed.

[[Page 54353]]



                                Table 1.--Subchronic, Chronic, and Other Toxicity
----------------------------------------------------------------------------------------------------------------
             Guideline No.                       Study Type                            Results
----------------------------------------------------------------------------------------------------------------
870.3100                                 90-Day oral toxicity, mice  NOAEL = 325.0 for males; 696.5 for females
                                                                      mg/kg/day
                                                                     LOAEL = 1,724.6 for males, 3,599.5 for
                                                                      females mg/kg/day based on elevated water
                                                                      intake and changes in hematological
                                                                      parameters (erythrocyte count, MCV) in
                                                                      males; increases in liver weights and
                                                                      plasma cholesterol in females.
----------------------------------------------------------------------------------------------------------------
870.3100                                 90-Day oral toxicity, rat   NOAEL = 372.7 for males; 561.4 for females
                                                                      mg/kg/day
                                                                     LOAEL = 1,524.0 for males, 2,585.9 for
                                                                      females mg/kg/day based on males: decrease
                                                                      in plasma triglycerides and increase in
                                                                      leukoyte counts, alkaline phosphatase
                                                                      levels, pale livers and increased relative
                                                                      liver weights; females: increased food
                                                                      intake, decreased body weight gain and
                                                                      food efficiency and increased plasma
                                                                      cholesterol levels.
----------------------------------------------------------------------------------------------------------------
870.3150                                 90-Day oral toxicity, dog   NOAEL = 9.1 mg/kg/day
                                                                     LOAEL = 62.5 mg/kg/day based on increased
                                                                      absolute and relative liver weight,
                                                                      hepatocellular hypertrophy, increased
                                                                      serum activity of activity of alkaline
                                                                      phosphatase and decreased plasma protein
                                                                      levels.
----------------------------------------------------------------------------------------------------------------
870.3700                                 Prenatal developmental in   Maternal NOAEL = 1,000 mg/kg/day
                                          rodents (rat)              LOAEL = >1,000 mg/kg/day based on the
                                                                      absence of treatment related toxicity in
                                                                      the dams at the highest dose tested.
                                                                     Developmental NOAEL = 1,000 mg/kg/day
                                                                     LOAEL = >1,000 mg/kg/day based on the
                                                                      absence of treatment related toxicity in
                                                                      the fetuses at the highest dose tested.
----------------------------------------------------------------------------------------------------------------
870.3700                                 Prenatal developmental in   Maternal NOAEL = 1,000 mg/kg/day
                                          nonrodents(rabbit)         LOAEL = >1,000 mg/kg/day based on the
                                                                      absence of treatment related toxicity in
                                                                      the dams at the highest dose tested.
                                                                     Developmental NOAEL = 1,000 mg/kg/day
                                                                     LOAEL = >1,000 mg/kg/day based on the
                                                                      absence of treatment related toxicity in
                                                                      the fetuses at the highest dose tested.
----------------------------------------------------------------------------------------------------------------
870.3800                                 Reproduction and fertility  Parental/Systemic NOAEL = 214.9 mg/kg/day
                                          effects, rat               LOAEL = 2,509 mg/kg/day based on increased
                                                                      relative liver weights in both sexes and
                                                                      bile duct proliferation in F0 and F1
                                                                      parental males.
                                                                     Reproductive NOAEL = 214.9 mg/kg/day
                                                                     LOAEL = 2,509 mg/kg/day based on decreased
                                                                      mean litter weight at day 28 (F1 and F2),
                                                                      reduced body weight development in F1 and
                                                                      F2 pups.
                                                                     Offspring NOAEL = 214.9 mg/kg/day
                                                                     LOAEL = 2,509 mg/kg/day based on reduced
                                                                      body weight development during lactation
                                                                      and increased relative liver weights of
                                                                      the pups.
----------------------------------------------------------------------------------------------------------------
870.4100                                 Chronic toxicity, dog       NOAEL = 2.62 mg/kg/day
                                                                     LOAEL = 24.69 mg/kg/day based on
                                                                      biochemical and morphological liver
                                                                      effects, e.g., swelling, distinct
                                                                      lobulation and discoloration, increases in
                                                                      absolute and relative liver weights, and
                                                                      activities of ALT and ALP, hepatocellular
                                                                      hypertrophy and periportal fatty change.
----------------------------------------------------------------------------------------------------------------
870.4200                                 Carcinogenicity, mice       NOAEL = 58.5 mg/kg/day
                                                                     LOAEL = 283.4 mg/kg/day based on increased
                                                                      blood urea nitrogen concentration,
                                                                      decreased kidney weights and
                                                                      histopathological changes in the kidneys.
                                                                      No evidence of carcinogenicity.
----------------------------------------------------------------------------------------------------------------
870.4300                                 Combined chronic toxicity/  NOAEL = 26.0 mg/kg/day
                                          Carcinogenicity, rats      LOAEL = 262.5 mg/kg/day based on
                                                                      histopathological changes in the liver
                                                                      (bile duct hyperplasia). Evidence of
                                                                      carcinogenicity, consisting of treatment-
                                                                      related rare and uncommon tumors in
                                                                      multiple organs/tissues in male and female
                                                                      rats.
----------------------------------------------------------------------------------------------------------------
870.5100                                 Gene mutation               Negative with and without S9 activation up
                                                                      to 5,000 micrograms/plate in bacterial
                                                                      reverse mutation test (S. typhimurium).
----------------------------------------------------------------------------------------------------------------
870.5300                                 In vitro mammalian cell     Negative with and without S9 activation up
                                          gene mutation               to 125 micrograms/mL (with S9) and 150
                                                                      micrograms/mL (without S9) in in vitro
                                                                      mammalian cell forward mutation test
                                                                      (Chinese hamster lung fibroblasts).
----------------------------------------------------------------------------------------------------------------
870.5375                                 In vitro mammalian          Negative with and without S9 activation up
                                          chromosomal aberration      to 150 micrograms/ml in in vitro mammalian
                                          tests                       cell assay (Chinese hamster ovary cells).
870.5385                                 Mammalian chromosomal       Negative at 2,000 mg/kg in in vivo bone
                                          aberration                  marrow micronucleus assay (mice).
----------------------------------------------------------------------------------------------------------------

[[Page 54354]]

 
870.5550                                 Unscheduled DNA synthesis   Negative up to 500 micrograms/ml in in
                                                                      vitro mammalian cell assay (rat primary
                                                                      hepatocytes).
----------------------------------------------------------------------------------------------------------------
870.6200                                 Acute neurotoxicity         NOAEL = 2,000 mg/kg/day
                                          screening battery, rat     LOAEL = >2,000 mg/kg/day based on no
                                                                      effects at the highest dose tested.
----------------------------------------------------------------------------------------------------------------
870.6200                                 Subchronic neurotoxicity    Systemic. NOAEL = 86.0 mg/kg/day
                                          screening battery          LOAEL = 342.0 mg/kg/day based on decreased
                                                                      body weight and increased food
                                                                      consumption.
                                                                     Neurotoxicity. NOAEL = 1,434 mg/kg/day for
                                                                      males and 2,314 mg/kg/day for females
                                                                     LOAEL = >1,434 mg/kg/day for males and
                                                                      >2314 mg/kg/day for females based on no
                                                                      effects at the highest dose tested.
----------------------------------------------------------------------------------------------------------------
870.7485                                 Metabolism and pharmaco-    Up to 99% excreted via urine and feces
                                          kinetics                    within 72 hours. Material metabolized
                                                                      extensively; small percentage passed
                                                                      through rat unchanged. Twelve metabolites
                                                                      identified. Proposed biotransformation
                                                                      pathway via oxidation of methyl group on
                                                                      aromatic ring, leading to carboxylic acid
                                                                      metabolite via hydroxymethyl-derivative.
----------------------------------------------------------------------------------------------------------------
                                         Special studies             28-Day Dietary - Dog: NOAEL was 3.0 mg/kg/
                                                                      day for males and 3.4 mg/kg/day for
                                                                      females. The LOAEL was 31.5 mg/kg/day for
                                                                      males and 35.0 mg/kg/day for females based
                                                                      on hepatocellular hypertrophy, vacuolated
                                                                      hepatocytes and elevated serum alkaline
                                                                      phosphatase activity.
                                                                     28-Day Dietary + 28-Day Recovery - Dog: The
                                                                      microsomal enzyme induction LOAEL was 2.93-
                                                                      3.01 mg/kg/day (the highest dose tested).
                                                                      The NOAEL was 0.77 mg/kg/day.
                                                                     Liver foci test for tumor initiating
                                                                      effects - Rats (males only): Negative for
                                                                      tumor initiating potential in rat liver.
                                                                     28-Day Dietary Rat: NOAEL = 579.3 mg/kg/day
                                                                      for males and 195.8 mg/kg/day for females.
                                                                      LOAEL=1,934.4 mg/kg/day for males and
                                                                      572.8 mg/kg/day for females based on
                                                                      increases in alkaline phosphatase,
                                                                      cholesterol and relative liver weights in
                                                                      males; increases in cholesterol and
                                                                      triglycerides as well as absolute and
                                                                      relative liver weights in females.
----------------------------------------------------------------------------------------------------------------

B. Toxicological Endpoints

    The dose at which no adverse effects are observed (the NOAEL) from 
the toxicology study identified as appropriate for use in risk 
assessment is used to estimate the toxicological level of concern 
(LOC). However, the lowest dose at which adverse effects of concern are 
identified (the LOAEL) is sometimes used for risk assessment if no 
NOAEL was achieved in the toxicology study selected. An uncertainty 
factor (UF) is applied to reflect uncertainties inherent in the 
extrapolation from laboratory animal data to humans and in the 
variations in sensitivity among members of the human population as well 
as other unknowns. An UF of 100 is routinely used, 10X to account for 
interspecies differences and 10X for intra species differences. No 
special uncertainty factors were appropriate or used in the dietary 
risk assessment.
    For dietary risk assessment (other than cancer) the Agency uses the 
UF to calculate an acute or chronic reference dose (acute RfD or 
chronic RfD) where the RfD is equal to the NOAEL divided by the 
appropriate UF (RfD = NOAEL/UF). Where an additional safety factor is 
retained due to concerns unique to the FQPA, this additional factor is 
applied to the RfD by dividing the RfD by such additional factor. The 
acute or chronic Population Adjusted Dose (aPAD or cPAD) is a 
modification of the RfD to accommodate this type of FQPA Safety Factor.
    For non-dietary risk assessments (other than cancer) the UF is used 
to determine the LOC. For example, when 100 is the appropriate UF (10X 
to account for interspecies differences and 10X for intraspecies 
differences) the LOC is 100. To estimate risk, a ratio of the NOAEL to 
exposures (margin of exposure (MOE) = NOAEL/exposure) is calculated and 
compared to the LOC. In this case because this is an import tolerance 
only, there is only dietary risk.
    The linear default risk methodology (Q1*) is the primary method 
currently used by the Agency to quantify carcinogenic risk. The Q1* 
approach assumes that any amount of exposure will lead to some degree 
of cancer risk. A Q1* is calculated and used to estimate risk which 
represents a probability of occurrence of additional cancer cases 
(e.g., risk is expressed as 1 x 10-6 or one in a 
million). Under certain specific circumstances, MOE calculations will 
be used for the carcinogenic risk assessment. In this non-linear 
approach, a ``point of departure'' is identified below which 
carcinogenic effects are not expected. The point of departure is 
typically a NOAEL based on an endpoint related to cancer effects though 
it may be a different value derived from the dose response curve. To 
estimate risk, a ratio of the point of departure to exposure 
(MOEcancer = point of departure/exposures) is calculated. A 
summary of the toxicological endpoints for iprovalicarb used for human 
risk assessment is shown in the following Table 2:

[[Page 54355]]



     Table 2.--Summary of Toxicological Dose and Endpoints for iprovalicarb for Use in Human Risk Assessment
----------------------------------------------------------------------------------------------------------------
                                                                FQPA SF\1\ and Level of
          Exposure Scenario               Dose Used in Risk         Concern for Risk     Study and Toxicological
                                            Assessment, UF             Assessment                Effects
----------------------------------------------------------------------------------------------------------------
Chronic Dietary all populations        NOAEL= 2.6 mg/kg/day     FQPA SF = 1X             1-Year Dog Study
                                       UF = 100 Chronic RfD =   cPAD = chronic RfD/FQPA  LOAEL = 24.69 mg/kg/day
                                        0.026 mg/kg/day.         SF = 0.026 mg/kg/day.    based on liver
                                                                                          effects: swelling,
                                                                                          enlargement, distinct
                                                                                          lobulation and
                                                                                          discoloration,
                                                                                          increased absolute and
                                                                                          relative liver
                                                                                          weights, and
                                                                                          accompanying
                                                                                          hepatocellular
                                                                                          hypertrophy and fatty
                                                                                          change, and elevated
                                                                                          serum liver enzyme
                                                                                          activities.
----------------------------------------------------------------------------------------------------------------
Cancer (oral)                          Q1* = 4.5 X 104 (mg/kg/    .....................  Combined chronic
                                        day)-1                                            toxicity/
                                                                                          carcinogenicity, two-
                                                                                          year rat study Q1*
                                                                                          based on the combined
                                                                                          follicular cell
                                                                                          adenomas and
                                                                                          carcinomas in the
                                                                                          thyroid gland of
                                                                                          female rats.
----------------------------------------------------------------------------------------------------------------
\1\ The reference to the FQPA Safety Factor refers to any additional safety factor retained due to concerns
  unique to the FQPA.

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. This is the first feed 
and/or food use for iprovalicarb in the United States. This activity 
reflects the establishment of a U.S. import tolerance on grape without 
a U.S. registration and therefore the only exposure that occurs is 
dietary. Risk assessments were conducted by EPA to assess dietary 
exposures from iprovalicarb in food as follows:
    i. Acute exposure. Acute dietary risk assessments are performed for 
a food-use pesticide if a toxicological study has indicated the 
possibility of an effect of concern occurring as a result of a one day 
or single exposure. Iprovalicarb is of low acute oral toxicity in rats 
with no adverse effects observed at doses well above the limit test 
dose (>5,000 mg/kg). In addition, rat and rabbit teratology studies and 
an acute neurotoxicity rat study, presented no effects indicative of 
early toxicity. Also, in sub-chronic feeding and reproduction toxicity 
studies, there were no treatment-related effects that could be 
attributable to a single dose. It is for these reasons that an acute 
analysis was not conducted, i. e., due to the lack of any appropriate 
toxicological end-point. Accordingly, an acute risk analysis was not 
appropriate and was not conducted.
    ii. Chronic exposure.In conducting this chronic dietary risk 
assessment the Dietary Exposure Evaluation Model (DEEM) 
analysis evaluated the individual food consumption as reported by 
respondents in the USDA 1989-1992 nationwide Continuing Surveys of Food 
Intake by Individuals (CSFII) and accumulated exposure to the chemical 
for each commodity. The following assumptions were made for the chronic 
exposure assessments: A DEEM chronic dietary exposure 
analysis was performed using tolerance residue levels and 100% crop 
treated. Data from a grape processing study indicated that iprovalicarb 
residues did not concentrate in grape processed commodities; therefore, 
the DEEM concentration factors for grape (i.e.: juice, juice-
concentrate, raisin) were set at 1, indicating no concentration of 
residues. The DEEM analysis included wine, sherry and raisin. 
EPA does not expect the chronic risk to exceed 100% of the cPAD, as 
shown in the following Table 3:

                             Table 3.--Chronic (Non-Cancer) Exposure to Iprovalicarb
----------------------------------------------------------------------------------------------------------------
                                                                Dietary exposure                        %cPAD
                     Population Subgroup                          (mg/kg/day)      cPAD (mg/kg/day)     (Food)
----------------------------------------------------------------------------------------------------------------
U.S. Population                                                         0.000688              0.026          2.6
----------------------------------------------------------------------------------------------------------------
All infants (<1 year old)                                               0.001282              0.026          4.9
----------------------------------------------------------------------------------------------------------------
Children (1-6 years old)                                                0.002443              0.026          9.3
----------------------------------------------------------------------------------------------------------------
Children (7-12 years old)                                               0.000668              0.026          2.6
----------------------------------------------------------------------------------------------------------------

    iii. Cancer. In accordance with the EPA Draft Guidelines for 
Carcinogen Risk Assessment (July, 1999) the Agency has classified 
iprovalicarb into the category ``Likely to be carcinogenic to humans'' 
based on the following weight-of-the-evidence considerations:
    Iprovalicarb induced rare and infrequently occurring tumors in 
Wistar rats. At the high dose, males developed malignant osteosarcomas 
and females also developed benign transitional cell papillomas of the 
urinary bladder. At the mid and high doses, females also developed 
malignant mixed Mullerian tumors of the uterus and follicular cell 
adenomas and carcinomas in the thyroid gland. Although the incidences 
of these tumors were low, they are rare or uncommon in Wistar rats. 
Most of these tumors were induced above the limit dose (1,000 mg/kg/
day) which was adequate and not excessively toxic. In mice, no 
treatment-related increase in tumors was observed in animals treated 
above the limit dose which was adequate and not excessively toxic.
    Iprovalicarb is not mutagenic. Although mechanistic studies 
suggested that iprovalicarb may not be a tumor initiator, these studies 
were inadequate to establish the definitive mode of action for tumor 
induction in rats.
    The Agency is using a linear low-dose extrapolation 
(Q1*) approach for estimating the human cancer risk based

[[Page 54356]]

on the most potent tumor in rats. This approach is supported by the 
lack of confirmation of the mode of action of iprovalicarb. The most 
potent Q1* for iprovalicarb was determined to be 4.5 x 
10-4 (mg/kg/day)-1 based on combined follicular 
cell adenomas and carcinomas in the thyroid gland of the female rat.
    Percent crop treated and/or anticipated residues were not used.
    2. Dietary exposure from drinking water. Residues in drinking water 
are not expected to result as a consequence of establishing an import 
tolerance for iprovalicarb residues in or on grape. Iprovalicarb is not 
registered for use in the United States. Therefore, exposures through 
drinking water is unlikely.
    3. From non-dietary exposure. The term ``residential exposure'' is 
used in this document to refer to non-occupational, non-dietary 
exposure (e.g., for lawn and garden pest control, indoor pest control, 
termiticides, and flea and tick control on pets).
    Iprovalicarb is not registered for use on any sites that would 
result in residential exposure.
    4. Cumulative exposure to substances with a common mechanism of 
toxicity. Section 408(b)(2)(D)(v) requires that, when considering 
whether to establish, modify, or revoke a tolerance, the Agency 
consider ``available information'' concerning the cumulative effects of 
a particular pesticide's residues and ``other substances that have a 
common mechanism of toxicity.''
    EPA does not have, at this time, available data to determine 
whether iprovalicarb has a common mechanism of toxicity with other 
substances or how to include this pesticide in a cumulative risk 
assessment. Unlike other pesticides for which EPA has followed a 
cumulative risk approach based on a common mechanism of toxicity, 
iprovalicarb does not appear to produce a toxic metabolite produced by 
other substances. For the purposes of this tolerance action, therefore, 
EPA has not assumed that iprovalicarb has a common mechanism of 
toxicity with other substances. For information regarding EPA's efforts 
to determine which chemicals have a common mechanism of toxicity and to 
evaluate the cumulative effects of such chemicals, see the final rule 
for Bifenthrin Pesticide Tolerances (62 FR 62961, November 26, 1997).

D. Safety Factor for Infants and Children

    1. In general. FFDCA section 408 provides that EPA shall apply an 
additional tenfold margin of safety for infants and children in the 
case of threshold effects to account for prenatal and postnatal 
toxicity and the completeness of the database on toxicity and exposure 
unless EPA determines that a different margin of safety will be safe 
for infants and children. Margins of safety are incorporated into EPA 
risk assessments either directly through use of a margin of exposure 
(MOE) analysis or through using uncertainty (safety) factors in 
calculating a dose level that poses no appreciable risk to humans.
    2. Prenatal and postnatal sensitivity. There is no evidence for 
increased susceptibility of fetuses to in utero exposure of 
iprovalicarb in either the rat developmental or rabbit developmental 
studies. In both studies, the NOAEL for both maternal and developmental 
toxicity was the highest dose tested.
    Based on the results in the 2-generation reproduction study in 
rats, a qualitative increased susceptibility of the neonates (as 
compared with adults) was demonstrated for iprovalicarb. The parental 
systemic NOAELs were based on decreased body weights and liver weights 
as well as bile duct proliferation; for females, the parental systemic 
NOAELs were based on increased relative liver weights. Reproductive 
LOAELs were not attained (greater than higest dose tested (HDT), limit 
dose). In offspring, the NOAELs were based on decreased mean litter 
weight on day 28, reduced body weight during lactation, and increased 
pup relative liver weights as well as reduced lactation index in 
F1. There was considered to be an increase in sensitivity of 
the neonates (as compared with adults) because of the lower lactation 
index (decreased pup survival) and decreased pup body weight. Although 
there is evidence of qualitative susceptibility in the 2-generation 
reproduction study, the Agency concludes that there is a low level of 
concern (and no residual uncertainty) because: (1) The increased 
susceptibility (decrease in pup survival) was seen only at the highest 
dose tested (2,074 mg/kg/day) which is twice the limit dose; (2) the 
decrease in pup survival was seen only in one generation 
(F1, not replicated in F2); (3) there are clearly 
defined NOAELs/LOAELs for parental and offspring toxicity; and (4) the 
effects seen in the offspring occurred at a much higher dose (192 mg/
kg/day) than that used to establish the chronic RFD (NOAEL of 2.6 mg/
kg/day).
    3. Conclusion. There is a complete toxicity database for an import 
tolerance for iprovalicarb and exposure data are complete or are 
estimated based on data that reasonably accounts for potential dietary 
exposures. The Agency concludes that there are reliable data that 
indicate there are no (residual) concerns for pre- and/or postnatal 
toxicity following exposure to iprovalicarb and therefore, no 
additional safety factor (1X) is necessary to protect the safety of 
infants and children.

E. Aggregate Risks and Determination of Safety

    1. Acute risk. Iprovalicarb is of low acute oral toxicity in rats 
with no adverse effects observed at doses well above the limit test 
dose (>5,000 mg/kg). In addition, rat and rabbit teratology studies and 
an acute neurotoxicity rat study, presented no effects indicative of 
early toxicity. Also, in sub-chronic feeding and reproduction toxicity 
studies, there were no treatment-related effects that could be 
attributable to a single dose. It is for these reasons that 
iprovalicarb is not expected to pose an acute risk.
    2. Chronic risk. Using the exposure assumptions described in this 
unit for chronic exposure, EPA has concluded that exposure to 
iprovalicarb from food will utilize 2.6% of the cPAD for the U.S. 
population, 4.9% of the cPAD for All infants (<1 year old), 9.3% of the 
cPAD for children 1-6 years old and 2.6% of the cPAD for children 7-12 
years old. There are no residential uses for iprovalicarb.
    In addition, there is not any potential for chronic dietary 
exposure to iprovalicarb in drinking water because the only use is an 
import tolerance. There are no U.S. registered products or uses at this 
time. EPA does not expect the aggregate exposure to exceed 100% of the 
cPAD, as shown in the following Table 4:

              Table 4.--Aggregate Risk Assessment for Chronic (Non-Cancer) Exposure to iprovalicarb
----------------------------------------------------------------------------------------------------------------
                                                                             Surface       Ground
              Population Subgroup                cPAD (mg/kg/    %cPAD      Water EEC    Water EEC     Chronic
                                                     day)        (Food)       (ppb)        (ppb)     DWLOC (ppb)
----------------------------------------------------------------------------------------------------------------
U.S. Population                                        0.026          2.6          N/A          N/A          N/A
----------------------------------------------------------------------------------------------------------------

[[Page 54357]]

 
All infants (<1 year old)                              0.026          4.9          N/A          N/A          N/A
----------------------------------------------------------------------------------------------------------------
Children (1-6 years old)                               0.026          9.3          N/A          N/A          N/A
----------------------------------------------------------------------------------------------------------------
Children (7-12 years old)                              0.026          2.6          N/A          N/A          N/A
----------------------------------------------------------------------------------------------------------------

    3. Short-term risk. Short-term aggregate exposure takes into 
account residential exposure plus chronic exposure to food and water 
(considered to be a background exposure level).
    Iprovalicarb is not registered for use on any sites that would 
result in residential exposure. Therefore, the aggregate risk is the 
sum of the risk from food and water, which do not exceed the Agency's 
level of concern. Residues in water, both surface and ground water, are 
expected to be zero because there are no U.S. uses, only this import 
tolerance for grape.
    4. Intermediate-term risk. Intermediate-term aggregate exposure 
takes into account residential exposure plus chronic exposure to food 
and water (considered to be a background exposure level).
    Iprovalicarb is not registered for use on any sites that would 
result in residential exposure. Therefore, the aggregate risk is the 
sum of the risk from food and water, which do not exceed the Agency's 
level of concern. Residues in water, both surface and ground water, are 
expected to be zero because there are no U.S. uses, only this import 
tolerance for grape.
    5. Aggregate cancer risk for U.S. population. The lifetime risk of 
developing cancer from iprovalicarb exposure is determined for the U.S. 
population (total) only. The estimated exposure to iprovalicarb is 
0.000688 mg/kg/day. Applying the Q1* of 4.5 x 
10-4 (mg/kg/day)-1 to the exposure value results 
in a cancer risk estimate of 3.1 x 10-7. This risk is 
negligible.
    6. Determination of safety. Based on these risk assessments, EPA 
concludes that there is a reasonable certainty that no harm will result 
to the general population, and to infants and children from aggregate 
exposure to iprovalicarb residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

    The enforcement analytical residue analytical method is an liquid 
chromotography/mass spectrometry method. The limit of quantitation is 
0.05 ppm in grape, wine, juice and raisin. Recovery and sensitivity of 
the method is considered adequate (95-114%).
    Adequate enforcement methodology (example--gas chromatography) is 
available to enforce the tolerance expression. The method may be 
requested from: Paul Golden, USEPA (7503C), Office of Pesticide 
Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW, 
Washington, DC 20460; telephone number: (410) 305-2960; e-mail address: 
www.epa.gov/oppbead1/methods/ (RAM Mailbox).

B. International Residue Limits

    No maximum residue levels have yet been established by the CODEX 
Alimentarius Commission for iprovalicarb in/on grape or raisin.

V. Conclusion

    Therefore, tolerances are established for residues of iprovalicarb, 
[2-methyl-1[[[(1S)-(4-methylphenyl)ethyl] amino]carbonyl] 
propyl]carbamic acid methylethylester, in or on grape at 2.0 ppm.

VI. Objections and Hearing Requests

    Under section 408(g) of the FFDCA, as amended by the FQPA, any 
person may file an objection to any aspect of this regulation and may 
also request a hearing on those objections. The EPA procedural 
regulations which govern the submission of objections and requests for 
hearings appear in 40 CFR part 178. Although the procedures in those 
regulations require some modification to reflect the amendments made to 
the FFDCA by the FQPA of 1996, EPA will continue to use those 
procedures, with appropriate adjustments, until the necessary 
modifications can be made. The new section 408(g) provides essentially 
the same process for persons to ``object'' to a regulation for an 
exemption from the requirement of a tolerance issued by EPA under new 
section 408(d), as was provided in the old FFDCA sections 408 and 409. 
However, the period for filing objections is now 60 days, rather than 
30 days.

A. What Do I Need to Do to File an Objection or Request a Hearing?

    You must file your objection or request a hearing on this 
regulation in accordance with the instructions provided in this unit 
and in 40 CFR part 178. To ensure proper receipt by EPA, you must 
identify docket control number OPP-2002-0203 in the subject line on the 
first page of your submission. All requests must be in writing, and 
must be mailed or delivered to the Hearing Clerk on or before October 
21, 2002.
    1. Filing the request. Your objection must specify the specific 
provisions in the regulation that you object to, and the grounds for 
the objections (40 CFR 178.25). If a hearing is requested, the 
objections must include a statement of the factual issues(s) on which a 
hearing is requested, the requestor's contentions on such issues, and a 
summary of any evidence relied upon by the objector (40 CFR 178.27). 
Information submitted in connection with an objection or hearing 
request may be claimed confidential by marking any part or all of that 
information as CBI. Information so marked will not be disclosed except 
in accordance with procedures set forth in 40 CFR part 2. A copy of the 
information that does not contain CBI must be submitted for inclusion 
in the public record. Information not marked confidential may be 
disclosed publicly by EPA without prior notice.
    Mail your written request to: Office of the Hearing Clerk (1900), 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460. You may also deliver your request to the Office 
of the Hearing Clerk in Rm. C400, Waterside Mall, 401 M St., SW., 
Washington, DC 20460. The Office of the Hearing Clerk is open from 8 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The 
telephone number for the Office of the Hearing Clerk is (202) 260-4865.
    2. Tolerance fee payment. If you file an objection or request a 
hearing, you must also pay the fee prescribed by 40 CFR 180.33(i) or 
request a waiver of that fee pursuant to 40 CFR 180.33(m). You must 
mail the fee to: EPA Headquarters

[[Page 54358]]

Accounting Operations Branch, Office of Pesticide Programs, P.O. Box 
360277M, Pittsburgh, PA 15251. Please identify the fee submission by 
labeling it ``Tolerance Petition Fees.''
    EPA is authorized to waive any fee requirement ``when in the 
judgement of the Administrator such a waiver or refund is equitable and 
not contrary to the purpose of this subsection.'' For additional 
information regarding the waiver of these fees, you may contact James 
Tompkins by phone at (703) 305-5697, by e-mail at [email protected], 
or by mailing a request for information to Mr. Tompkins at Registration 
Division (7505C), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
    If you would like to request a waiver of the tolerance objection 
fees, you must mail your request for such a waiver to: James Hollins, 
Information Resources and Services Division (7502C), Office of 
Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania 
Ave., NW., Washington, DC 20460.
    3. Copies for the Docket. In addition to filing an objection or 
hearing request with the Hearing Clerk as described in Unit VI.A., you 
should also send a copy of your request to the PIRIB for its inclusion 
in the official record that is described in Unit I.B.2. Mail your 
copies, identified by docket control number OPP-2002-0203, to: Public 
Information and Records Integrity Branch, Information Resources and 
Services Division (7502C), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460. 
In person or by courier, bring a copy to the location of the PIRIB 
described in Unit I.B.2. You may also send an electronic copy of your 
request via e-mail to: [email protected]. Please use an ASCII file 
format and avoid the use of special characters and any form of 
encryption. Copies of electronic objections and hearing requests will 
also be accepted on disks in WordPerfect 6.1/8.0 or ASCII file format. 
Do not include any CBI in your electronic copy. You may also submit an 
electronic copy of your request at many Federal Depository Libraries.

B. When Will the Agency Grant a Request for a Hearing?

    A request for a hearing will be granted if the Administrator 
determines that the material submitted shows the following: There is a 
genuine and substantial issue of fact; there is a reasonable 
possibility that available evidence identified by the requestor would, 
if established resolve one or more of such issues in favor of the 
requestor, taking into account uncontested claims or facts to the 
contrary; and resolution of the factual issues(s) in the manner sought 
by the requestor would be adequate to justify the action requested (40 
CFR 178.32).

VII. Regulatory Assessment Requirements

    This final rule establishes a tolerance under FFDCA section 408(d) 
in response to a petition submitted to the Agency. The Office of 
Management and Budget (OMB) has exempted these types of actions from 
review under Executive Order 12866, entitled Regulatory Planning and 
Review (58 FR 51735, October 4, 1993). Because this rule has been 
exempted from review under Executive Order 12866 due to its lack of 
significance, this rule is not subject to Executive Order 13211, 
Actions Concerning Regulations That Significantly Affect Energy Supply, 
Distribution, or Use (66 FR 28355, May 22, 2001). This final rule does 
not contain any information collections subject to OMB approval under 
the Paperwork Reduction Act (PRA), 44 U.S.C. 3501 et seq., or impose 
any enforceable duty or contain any unfunded mandate as described under 
Title II of the Unfunded Mandates Reform Act of 1995 (UMRA) (Public Law 
104-4). Nor does it require any special considerations under Executive 
Order 12898, entitled Federal Actions to Address Environmental Justice 
in Minority Populations and Low-Income Populations (59 FR 7629, 
February 16, 1994); or OMB review or any Agency action under Executive 
Order 13045, entitled Protection of Children from Environmental Health 
Risks and Safety Risks (62 FR 19885, April 23, 1997). This action does 
not involve any technical standards that would require Agency 
consideration of voluntary consensus standards pursuant to section 
12(d) of the National Technology Transfer and Advancement Act of 1995 
(NTTAA), Public Law 104-113, section 12(d) (15 U.S.C. 272 note). Since 
tolerances and exemptions that are established on the basis of a 
petition under FFDCA section 408(d), such as the tolerance in this 
final rule, do not require the issuance of a proposed rule, the 
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et 
seq.) do not apply. In addition, the Agency has determined that this 
action will not have a substantial direct effect on States, on the 
relationship between the national government and the States, or on the 
distribution of power and responsibilities among the various levels of 
government, as specified in Executive Order 13132, entitled Federalism 
(64 FR 43255, August 10, 1999). Executive Order 13132 requires EPA to 
develop an accountable process to ensure ``meaningful and timely input 
by State and local officials in the development of regulatory policies 
that have federalism implications.'' ``Policies that have federalism 
implications'' is defined in the Executive order to include regulations 
that have ``substantial direct effects on the States, on the 
relationship between the national government and the States, or on the 
distribution of power and responsibilities among the various levels of 
government.'' This final rule directly regulates growers, food 
processors, food handlers and food retailers, not States. This action 
does not alter the relationships or distribution of power and 
responsibilities established by Congress in the preemption provisions 
of FFDCA section 408(n)(4). For these same reasons, the Agency has 
determined that this rule does not have any ``tribal implications'' as 
described in Executive Order 13175, entitled Consultation and 
Coordination with Indian Tribal Governments (65 FR 67249, November 6, 
2000). Executive Order 13175, requires EPA to develop an accountable 
process to ensure ``meaningful and timely input by tribal officials in 
the development of regulatory policies that have tribal implications.'' 
``Policies that have tribal implications'' is defined in the Executive 
order to include regulations that have ``substantial direct effects on 
one or more Indian tribes, on the relationship between the Federal 
Government and the Indian tribes, or on the distribution of power and 
responsibilities between the Federal Government and Indian tribes.'' 
This rule will not have substantial direct effects on tribal 
governments, on the relationship between the Federal Government and 
Indian tribes, or on the distribution of power and responsibilities 
between the Federal Government and Indian tribes, as specified in 
Executive Order 13175. Thus, Executive Order 13175 does not apply to 
this rule.

VIII. Submission to Congress and the Comptroller General

    The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the 
Small Business Regulatory Enforcement Fairness Act of 1996, generally 
provides that before a rule may take effect, the agency promulgating 
the rule must submit a rule report, which includes a copy of the rule, 
to each House of the Congress and to the Comptroller General of the 
United States. EPA will submit a report containing this rule and other

[[Page 54359]]

required information to the U.S. Senate, the U.S. House of 
Representatives, and the Comptroller General of the United States prior 
to publication of this final rule in the Federal Register. This final 
rule is not a ``major rule'' as defined by 5 U.S.C. 804(2).

List of Subjects in 40 CFR Part 180

    Environmental protection, Administrative practice and procedure, 
Agricultural commodities, Pesticides and pests, Reporting and record 
keeping requirements.

    Dated:August 15, 2002.
Joseph J. Merenda,
Acting Director, Office of Pesticide Programs.

    Therefore, 40 CFR chapter I is amended as follows:

PART 180--[AMENDED]

    1. The authority citation for part 180 continues to read as 
follows:

    Authority: 21 U.S.C. 321(q), 346(a) and 374.


    2. Section 180.581 is added to read as follows:


Sec. 180.581  Iprovalicarb; tolerances for residues.

    (a) General. Tolerances are established for residues of 
iprovalicarb, [2-methyl-1[[[(1S)-(4-methylphenyl) ethyl] 
amino]carbonyl] propyl]carbamic acid methylethylester, in or on the 
following commodities.

------------------------------------------------------------------------
                   Commodity                        Parts per million
------------------------------------------------------------------------
Grape\1\                                                             2.0
------------------------------------------------------------------------
\1\ No U.S. registration as of July 31, 2002.

    (b) Section 18 emergency exemptions. [Reserved]
    (c) Tolerances with regional registrations. [Reserved]
    (d) Indirect or inadvertent residues. [Reserved]
[FR Doc. 02-21293 Filed 8-21-02; 8:45 am]
BILLING CODE 6560-50-S